Considerable interest has been shown in recent years in the essential fatty acids, primarily the acids of the n-6 series both as such and in relation to prostaglandin metabolism, but also the acids of the n-3 series.
The n-6 acids in particular are required in the body for the structure of membranes in and around cells, being believed to be necessary in particular for maintaining normal flexibility, fluidity and permeability of such membranes.
The pathways of metabolism of the n-6 essential fatty acids and the related n-3 acids sharing, it is believed, common enzymes in the two pathways, are: ##STR1## The pathways are not reversible nor, in man, are n-3 and n-6 series acids interconvertible.
These acids, which naturally are of all-cis configuration are systematically named as derivatives of the corresponding octadecanoic, eicosanoic or docosanoic acids e.g. .DELTA..sup.9,12 -octadecadienoic acid or .DELTA..sup.4,7,10,13,16,19 docosahexaenoic acid, but the numerical designation such as, correspondingly, 18:2 n-6 or 22:6 n-3 is convenient. Initials, for example, DHA for 22:6 n-3 (docosahexanaenoic acid), are also used but do not serve when n-3 and n-6 acids of the same chain length and degree of unsaturation exist. Trivial names in more or less common use in the n-6 series are as shown. Of the n-3 series only 18:3 n-3 has a commonly used trivial name, .alpha.-linolenic acid. It was characterised earlier than .gamma.-linolenic acid and reference in the literature simply to linolenic acid, especially in the earlier literature is to the .alpha.-acid.
In the body, the n-3 acids are metabolised preferentially and as a result, in plasma for example, levels of .alpha.-linolenic acid (18:3 n-3) are low and 18:4 n-3 and 20:4 n-3 are in trace amounts only. In contrast the n-6 acids are normally present in moderate amounts, though .gamma.-linolenic acid (GLA) is at low levels, being apparently converted to dihomo-.gamma.-linolenic acid (DGLA) more rapidly than its relatively slow production from linoleic acid. In both series the elongation stages in the metabolic pathways are much more rapid than the desaturations.
Considering dietary requirements in the n-6 series, it is well known, for example, that linoleic acid cannot be made by the body and so must be taken in the diet. However, it has been generally thought that the body can metabolise linoleic acid to all the other n-6 acids and therefore that provided linoleic acid intake is adequate, no lack of the other n-6 acids will be found. However, in previous patent applications of the present inventor, (for example published European Application No. A 0 003 407, U.S. Pat. No. 4 273 763; published European Patent Application No. A 0 004 770, U.S. Pat. No. 4 309 415; published European Application No. 0 019 423, U.S. Pat. No. 4 388 324) it has been pointed out that this is not so and that the first enzyme in the pathway, the .DELTA.-6 desaturase which, for example, converts linoleic acid to .gamma.-linolenic acid, is not fully effective in a variety of conditions. The administration of .gamma.-linolenic acid or dihomo-.gamma.-linolenic acid or both has been suggested and has been successful in treating a variety of clinical conditions.